Search PubMed⌕ Search

Biomedical subjects

V N Luine

Publications and source records attributed to V N Luine.

At least 37 records · Page 2Linked to original sources

Sexual behavior of male rats is differentially affected by timing of perinatal ACTH administration.

The laboratory rat was used as a model to investigate the effect of pre- and/or postnatal ACTH administration on sexual differentiation of the brain. Pregnant Sprague-Dawley rats were injected with ACTH 1-24 (10 micrograms/kg/2x/day or 500 micrograms/kg/2x/day); postnatally treated neonates were injected with the above dosages once a day. Perinatal treatment with ACTH (10 micrograms/kg/2x/day) altered several sexual behavior measurements, but did not have an overall effect on the number of males that exhibited sexual behavior. At a higher dose (500 micrograms/kg/2x/day) prenatal ACTH administration decreased sexual behavior in male rats, as measured by an increase in the percent of males that did not mount or intromit. In contrast, all males treated postnatally with ACTH (500 micrograms/kg/2x/day) completed 2 ejaculatory series and initiated a third series. No significant differences were observed in adult plasma testosterone or prolactin levels; however, serotonin levels in the preoptic area of adult male rats treated prenatally with ACTH (500 micrograms/kg/2x/day) were significantly higher than in prenatally treated saline males. In addition, an increase in plasma ACTH in adulthood was observed in animals injected postnatally with saline. This study indicates that the decrease in sexual behavior observed in males treated prenatally with ACTH is associated with increased serotonin levels in the preoptic area, which suggests that ACTH may act as a neuromodulator during sexual differentiation of the brain. It also demonstrates that the effect of perinatal manipulations on the development of male sexual behavior may vary depending on the ontogenetic period of the brain.

Adrenocorticotropic Hormone↗

Testosterone locally increases vasopressin content but fails to restore choline acetyltransferase activity in other regions in the senescent male rat brain.

Age-related decreases have been reported in both vasopressinergic and cholinergic innervation in the rat brain. Since both systems are also sensitive to sex steroids, the effect of testosterone supplementation on vasopressin (AVP) levels and on choline acetyltransferase (ChAT) activity was investigated in the brains of young, middle-aged and aged male rats. Although no age-related changes in AVP levels were observed in the lateral septum or the medial amygdala (MA), peripheral testosterone administration raised AVP levels in the MA in all age groups. ChAT activity decreased with age in the medial preoptic area and was not restored by testosterone.

Aging↗

Corticosterone-dependent alterations in utilization of catecholamines in discrete areas of rat brain.

This study investigated the impact of chronic adrenalectomy (ADX), and subsequent corticosterone (CORT) replacement to ADX rats, on brain levels of norepinephrine (NE) and dopamine (DA) and their extent of depletion after alpha-methyl-p-tyrosine (alpha-MpT) administration. Seven discrete hypothalamic areas, namely, the paraventricular nucleus (PVN), medial preoptic nucleus (POM), dorsomedial nucleus (DMN), ventromedial hypothalamus (VMH), perifornical lateral hypothalamus (PLH), supraoptic nucleus (SON), and arcuate nucleus/median eminence (ARC-ME), were examined. The steady-state content of NE and DA in all areas remained essentially unaltered 7 days after ablation of the adrenal glands, as well as after subsequent CORT replacement therapy in ADX rats. However, ADX, which reduced circulating CORT levels to 0.3 microgram % as compared to greater than 3.0 micrograms % in sham rats, caused a significant increase in the depletion of NE following alpha-MpT treatment, in 4 out of the 7 brain sites examined (PVN, PLH, DMN and ARC-ME). In these brain sites, the NE turnover rate (K, pg/microgram protein/h) and rate constant (K, h-1) increased following ADX. The chronic subcutaneous CORT implant (200 mg), which raised circulating CORT levels of ADX rats to 11 micrograms %, prevented this enhancement of NE turnover in the PVN, PLH and ARC-ME, but not the DMN. Unlike NE, DA utilization in the 7 discrete hypothalamic areas of alpha-MpT-treated rats remained unaltered after ablation of the adrenal glands, as well as after the CORT replacement therapy in ADX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Antibodies in serum of patients with Alzheimer's disease cause immunolysis of cholinergic nerve terminals from the rat cerebral cortex.

A blind study showing that serum from patients with Alzheimer's disease causes immunolysis of mammalian brain synaptosomes is reported. Control, aged-matched, sera were largely without effect. The immunolysis was directed mainly against cholinergic synaptosomes. The data support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged↗

Evidence for the presence of antibodies to cholinergic neurons in the serum of patients with Alzheimer's disease.

A blind study showing that serum from patients with Alzheimer's disease causes immunolysis of mammalian brain synaptosomes is reported. Control, aged-matched, sera were largely without effect. The immunolysis was directed mainly against cholinergic synaptosomes. The data presented support the hypothesis that autoimmune mechanisms may operate in the pathogenesis of Alzheimer's disease.

Aged↗

Hypothalamic serotonin lesions unmask hormone responsiveness of lordosis behavior in adult male rats.

Hypothalamic lesions of serotoninergic afferents following bilateral stereotoxic injections of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the region of the ventromedial hypothalamus enhanced the effects of hormonally induced lordosis responding in both male and female rats. However, similarities and differences in the enhanced responsiveness to ovarian hormones were observed between the sexes. Compared with sham-lesioned controls, lesioned males displayed elevated lordosis responding to estradiol (E) priming alone, as well as to priming with E followed by progresterone (P). On the other hand, lesioned females displayed elevated lordosis in response to E priming alone, but were not different from controls in a synergistic facilitation of lordosis by P after E priming. With respect to receptivity, neither lesioned nor control males displayed ear-wiggling and hop-darting in response to E + P, whereas both lesioned and control females were proceptive following this treatment. Therefore, hypothalamic lesions following 5,7-DHT increase lordosis, but fail to unmask in males the responsiveness to E + P priming proceptive behaviours by females. Further, the levels of lordosis responding displayed by lesioned males are lower than those of either lesioned or control females after E + P priming, as well as those of lesioned females after E priming alone, thus indicating that other inhibitory mechanisms continue to operate in the lesioned males.

Animals↗

Effects of hypothalamic serotonin depletion on lordosis behavior and gonadal hormone receptors.

The effects of chronic depletion of serotonin on feminine sexual behavior (lordosis), cytosolic progestin receptors and estradiol nuclear receptors were investigated. Intrahypothalamic administration of 5,7-dihydroxytryptamine (5,7-DHT) markedly enhanced lordotic responding in estradiol benzoate (EB)-primed, 5,7-DHT-treated female rats and in EB-progesterone primed, 5,7-DHT-treated male rats. Cytosolic progestin receptors were measured in preoptic-hypothalamic nuclei related to reproductive function in sham and 5,7-DHT-treated rats after EB priming. In both sexes, no differences between sham and 5,7-DHT-treated subjects were noted for progestin binding in the medial preoptic nucleus, ventromedial nucleus or arcuate-median eminence area. Estrogen-nuclear complexes were measured in the same brain nuclei of female rats following EB priming, and no differences between sham and 5,7-DHT-treated rats were found. Under the conditions employed, it would appear that, despite marked elevations in lordotic responsivity, the accumulation of estrogen nuclear receptors and the levels of estrogen inducible progestin receptors remain unaltered after chronic depletion of serotonin. Thus, serotonergic influences on lordosis do not appear to involve changes in the expression of steroid receptor levels in preoptic-hypothalamic nuclei known to mediate hormone-dependent neuroendocrine processes.

5,7-Dihydroxytryptamine↗

Temporal effects of intrahypothalamic 5,7-dihydroxytryptamine: relationship between serotonin levels and [3H]serotonin binding.

The relationship between serotonin (5-HT) levels and [3H]5-HT binding in discrete hypothalamic areas was examined in separate groups of animals at various times, following unilateral intrahypothalamic injection of 5,7-dihydroxytryptamine (5,7-DHT). Seven days post-5,7-DHT lesion, 5-HT levels were significantly decreased in both the ipsilateral and contralateral ventromedial and dorsomedial hypothalamic nuclei (VMN, DMN). In the lateral hypothalamic area (LHA), 5-HT levels were significantly decreased only ipsilaterally. Fifty days postlesion, 5-HT levels in the ipsilateral VMN remained significantly below sham, while the DMN and LHA returned to sham values. Seven days after 5,7-DHT there was a significant increase in [3H]5-HT labeling densities in the ipsilateral and contralateral ventromedial hypothalamic area as well as in the ipsilateral LHA. In contrast, in the dorsomedial hypothalamic area there was no increase in [3H]5-HT binding. Fifty days postlesion, no significant differences in [3H]5-HT binding between 5,7-DHT and sham were observed in any areas examined. This data provides further evidence for the regeneration of 5-HT fibers in the hypothalamus and demonstrates that the relationship between [3H]5-HT binding and 5-HT levels varies from one hypothalamic area to another.

5,7-Dihydroxytryptamine↗

Serotonin and 5-hydroxyindoleacetic acid levels in discrete hypothalamic areas of the rat brain: relation to circulating corticosterone.

We examined the influence of adrenalectomy (ADX), and chronic corticosterone (CORT) replacement, on serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels in discrete hypothalamic areas of the rat brain. A significant decrease in 5-HT (-25%) and 5-HIAA (-28%) content was observed in the paraventricular nucleus (PVN) 7 days following ADX. A similar decrease in 5-HT levels (-27%) was observed in the preoptic area (POM) following ADX. In contrast, 5-HT and 5-HIAA levels in the supraoptic nucleus (SON) were significantly elevated by 82% and 54%, respectively. Replacement therapy with subcutaneous CORT implants (200 mg) was effective in preventing these effects of ADX in some cases. These findings suggest that the pituitary-adrenal endocrine system may influence various physiological and behavioral functions via its action on serotonergic neurons within specific hypothalamic sites.

Adrenalectomy↗

Noradrenergic regulation of alpha 1-receptors during the postnatal development of the guinea pig.

In guinea pig brain, alpha 1-noradrenergic receptor concentrations undergo region-specific fluctuations during the first weeks of postnatal life. However, the factors involved in the regulation of these receptors have yet to be identified. In this study, the ontogeny of one possible regulatory factor, norepinephrine, was examined in relation to postnatal changes in alpha 1-receptor levels in several different regions of guinea pig brain. Results from these studies showed that while the activity of the noradrenergic system increased throughout the first weeks of postnatal development in each brain area examined, the concentration of alpha 1-receptors decreased in preoptic area and hypothalamus and increased in cortex. In subsequent experiments, the effects of noradrenergic lesions with 6-hydroxydopamine on alpha 1-receptor levels were assessed to examine the possibility that alpha 1-receptors are differentially sensitive to noradrenergic stimulation in cortex and preoptic area/hypothalamus in immature guinea pigs. Noradrenergic lesions which reduced norepinephrine levels by 87-94% resulted in significant elevations in alpha 1-receptors in all regions examined. These results are discussed with reference to the anatomical distribution of alpha 1-receptors and their regulation by norepinephrine.

Animals↗

Effect of progesterone on monoamine turnover in the brain of the estrogen-primed rat.

The effect of progesterone (P) on monoamine levels and turnover was evaluated in 8 brain nuclei in estrogen-primed rats. Animals were subcutaneously (SC) injected with P or vehicle 21 hours after SC treatment with 5 micrograms of estradiol benzoate (EB). EB-primed animals treated with P showed high levels of lordosis behavior and an LH surge three hours later. Initial concentrations of norepinephrine (NE), dopamine (DA), serotonin (5HT) and 5-hydroxyindole acetic acid were determined in EB-saline treated controls 3 hours after P or vehicle. NE and DA turnover was estimated from the exponential decline of these amines 2 hours after IP injection of alpha-methyl-p-tyrosine (5 hours after P or vehicle). The accumulation of 5HT 20 min following IP injection of pargyline was used as an index of 5HT turnover. P did not affect the initial NE, 5HT or 5HIAA concentrations in any of the brain nuclei studied, but decreased DA content in the arcuate-median eminence region (Ar-ME). The DA rate constant was elevated in the nucleus of the diagonal band of Broca and the DA turnover rate was decreased in the Ar-ME. In the periventricular region (PVE, anterior hypothalamic level) the NE turnover rate (K, pg/microgram protein/hr) and rate constant (k, hr-1) decreased following P treatment. Progesterone treatment decreased the accumulation of 5HT in the ventromedial hypothalamus (VMN, pars lateralis) and the dorsal midbrain central grey (MCG). Progesterone effects on monoamine turnover were not found in the lateral septal, medial preoptic, anterior hypothalamic or dorsal raphe nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Monoamine levels and turnover in brain: relationship to priming actions of estrogen.

Norepinephrine (NE), dopamine (DA) and serotonin (5HT) levels and turnover rates were studied in 8 discrete brain nuclei of ovariectomized rats 24 hours after the administration of 5 microgram of estradiol benzoate (EB) or sesame oil vehicle. This estrogen paradigm, by itself, did not induce sexual behavior or alter LH levels at the time these parameters were evaluated. However, combined with progesterone, the estrogen treatment was sufficient to generate an LH surge and induce sexual receptivity. Steady state concentrations of NE were significantly higher in the diagonal band of Broca (NDB) and the periventricular nucleus (PVE2; anterior hypothalamic level) following EB treatment. In addition, 5-hydroxyindole acetic acid (5HIAA) concentrations were elevated in the dorsal raphe of EB treated animals. Estrogen did not affect steady state concentrations of DA or 5HT in any of the brain nuclei studied. Turnover rates (K, pg/microgram protein/hr) and rate constants (k, hr-1) for NE were increased in the lateral septum (K, 140%; k, 120%), NDB (K, 160%; k, 130%) and the PVE2 (K, 140%; k, 70%) in EB treated animals. Estrogen decreased the rate constant for NE by 30% in the medial preoptic area. In contrast, DA and 5HT turnover rates were not significantly affected by estrogen. These results localize sites where estrogen induces changes in noradrenergic activity and suggest that these changes may be involved in the priming action of the steroid in inducing sexual behavior and/or gonadotropin secretion.

Animals↗

1,25-Dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei.

To better understand the role of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in brain function, the level of calcium-binding protein (CaBP) and the activities of choline acetyltransferase (CAT) and monoamine oxidase were measured in discrete brain nuclei of vitamin D-deficient and -replete male rats. The nuclei sampled were those in which receptors for 1,25-(OH)2D3 and/or vitamin D-dependent CaBP have been localized. Significant elevations in CAT activity were found in the arcuatemedian eminence and in the bed nucleus of the stria terminalis of rats made vitamin D replete by eight daily ip injections of 100 or 200 ng 1,25-(OH)2D3 as well as by constant intraventricular (ivi) infusion of 25 ng 1,25-(OH)2D3 for 7 days. The percent increase ranged from 12-45% and was related to the ip dose administered. Constant ivi of 2 mM CA2+ or 125 ng 25-hydroxyvitamin D3/day for 7 days did not alter CAT activity. No significant changes in monoamine oxidase or CaBP in discrete brain nuclei were observed with vitamin D repletion. Since the arcuate-median eminence of the hypothalamus is an important regulatory site in the neuroendocrine control of reproduction, serum testosterone was measured. Serum testosterone levels were abnormally low in the vitamin D-deficient animals, but increased 2- to 5-fold to normal values in those rats made vitamin D replete by constant ivi of 25 ng 1,25-(OH)2D3 or by ip injection of 100 or 200 ng 1,25-(OH)2D3. Patterns of serum LH paralleled those for testosterone. Our results suggest that 1,25-(OH)2D3 effects cholinergic activity in several discrete brain regions and may play a role in the neuroendocrine regulation of certain aspects of anterior pituitary gland function.

Animals↗

Sex-dependent differences in estrogen regulation of choline acetyltransferase are altered by neonatal treatments.

We investigated whether estrogenic actions of testosterone during development which mediate the suppression of feminine reproductive behavior and cyclic gonadotropin secretion also contribute to reported sex differences in the induction of choline acetyltransferase (ChAT) after estrogen priming in the diagonal band region of the preoptic area. Newborn female rats received estradiol (E2 females); newborn males received 1,4,6-androstatrien-3,17-dione (ATD), an inhibitor of aromatase (ATD males); and some of both sexes received vehicle treatment (control). In adulthood, feminine sexual behavior (lordosis) was tested after E2 plus progesterone priming. The neonatal treatments reversed the sex-specific response pattern; E2 females were defeminized and displayed minimal lordosis, as did control males, while ATD males showed maximal lordosis, as did control females. E2 was then administered, and ChAT activity was measured in the horizontal and vertical nuclei of the diagonal bands (hDB and vDB, respectively). Controls exhibited the normal sex-specific response to E2. Females showed increased ChAT activity in the hDB and unaltered activity in the vDB: males had unaltered ChAT activity in the hDB and decreased activity in the vDB. In neonatally treated males and females, ChAT activity after E2 administration was not altered from the normal sex-specific pattern in the hDB, i.e. all females showed increased hDB ChAT after E2, and no male responded. In the vDB, groups defeminized in terms of lordosis (E2 females and control males) showed higher ChAT activity in the absence of E2 priming, and E2 treatment decreased vDB ChAT in these groups. In addition, ATD males showed a unique response to E2 in the vDB, namely increased ChAT activity. Although neonatal E2 and ATD treatments did not completely reverse the sex-specific pattern of E2 priming on ChAT activity, the results obtained suggest that a net increase in diagonal band cholinergic function, as indexed by increased ChAT activity after E2 priming, may contribute to the ability of hormones to induce lordosis and/or LH surges.

Androstatrienes↗

Sex differences in long-term gonadectomized rats: monoamine levels and [3H]nitroimipramine binding in brain nuclei.

The levels of norepinephrine, dopamine, serotonin and the serotonin metabolite 5-hydroxyindoleacetic acid were measured in microdissected brain nuclei from long-term gonadectomized male and female rats. Females had 50 and 120% higher levels of serotonin in the anterior hypothalamic nucleus (AH) and arcuate-median eminence (AR-ME), respectively. No significant differences in norepinephrine, dopamine or 5-hydroxyindoline acetic acid were found in any of the brain nuclei sampled. The differences in serotonin content do not appear to result from a sexually dimorphic distribution of serotonin nerve terminals since quantitative autoradiography of 3H-nitroimipramine revealed no differences in binding between the sexes in the AH or AR-ME.

Animals↗

Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats.

Administration of estradiol to gonadectomized female, but not male rats, is associated with increased activity of choline acetyltransferase in the medial aspect of the horizontal diagonal band nucleus, the frontal cortex, and CA1 of the dorsal hippocampus. Four other basal forebrain cholinergic nuclei did not show changes in choline acetyltransferase activity after estradiol. These data have implications for possible benefits of estradiol administration to patients with senile dementia of the Alzheimer's type.

Animals↗

Naltrexone facilitation of sexual receptivity in the rat.

Naltrexone hydrochloride (3mg/kg) facilitated sexual receptivity in ovariectomized female rats given estradiol benzoate 44 hr previously. The latency of naltrexone facilitation is 3 hr, which is similar to that by progesterone. Other doses of naltrexone (1 and 5 mg/kg) were ineffective. Unlike the effect of progesterone, the facilitation of behavior by naltrexone is not blocked by the protein synthesis inhibitor anisomycin. Naltrexone facilitation was blocked by pargyline, a monoamine oxidase inhibitor.

Adrenalectomy↗

Facilitated sexual behavior reversed and serotonin restored by raphe nuclei transplanted into denervated hypothalamus.

Fetal raphe cells transplanted into the hypothalamus reversed facilitation of feminine sexual behavior in rats with brain lesions induced by 5,7-dihydroxytryptamine. Immunocytochemical and chemical analyses of serotonin indicate that reinnervation of the ventromedial nucleus of the hypothalamus by the transplants is associated with behavioral recovery. The findings suggest that transplanted fetal tissue can exert functional regulation over an innate, complex, hormone-dependent behavior in adult rats.

5,7-Dihydroxytryptamine↗